The candidate is a physician trained in Internal Medicine with subspecialty training in Infectious Diseases. She is currently a postdoctoral fellow in Dr. Ehrenfeld's laboratory studying Hepatitis A virus (HAV), an enterically-transmitted agent of epidemic jaundice. The research project focuses on the hypothesis that RNA replication of HAV is a rate-limiting step in virus growth, contributing to its slow infection cycle and minimal impact on host cell metabolism in cultured cells, a phenotype which differentiates it from the other members of its picomavirus family. Experiments are designed to characterize the HAV polymerase and other nonstructural viral proteins involved in RNA replication. The polymerase will be expressed in E. coli and its activity will be characterized through a mutational analysis. Protein-RNA interactions between host cell and viral proteins and the HAV genome and protein-protein interactions between these proteins and the putative HAV polymerase (3D protein) will be investigated with various crosslinking methods. Mutational analysis of 3D protein regions involved in these interactions is planned. The role of polymerase, other nonstructural proteins, and host cell proteins in RNA replication will also be studied in HAV-infected cells in culture. Because viral RNA replication in cultured cells is slow, replicons (self-replicating, subgenomic viral RNAs) will be constructed to facilitate the mutational analysis of viral proteins and viral RNA sequence and/or structure required for replication. The project will be done in the sponsor's laboratory in the Department of Cellular, Viral and Molecular Biology (CVMB), a research department in the School of Medicine closely allied to the Departments of Biochemistry, Biology, Human Genetics and Pathology through a combined graduate program in Molecular Biology. Frequent seminars with invited speakers are hosted by the combined program and weekly Journal Club and Research in Progress meetings in this department facilitate exchange of ideas, techniques and reagents. In addition, regular lab meetings and daily interaction with other postdoctoral fellows and graduate students in the laboratory contribute to an intellectually stimulating environment.